258 research outputs found

    Rapid Evolution of Sex-Pheromone-producing Enzyme in Drosophila

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    A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies. Long-chain cuticular hydrocarbons (e.g., dienes) are produced female-specifically, notably via the activity of the desaturase DESAT-F, and are potent pheromones for male courtship behavior in Drosophila melanogaster. We show that across the genus Drosophila, the expression of this enzyme is correlated with long-chain diene production and has undergone an extraordinary number of evolutionary transitions, including six independent gene inactivations, three losses of expression without gene loss, and two transitions in sex-specificity. Furthermore, we show that evolutionary transitions from monomorphism to dimorphism (and its reversion) in desatF expression involved the gain (and the inactivation) of a binding-site for the sex-determination transcription factor, DOUBLESEX. In addition, we documented a surprising example of the gain of particular cis-regulatory motifs of the desatF locus via a set of small deletions. Together, our results suggest that frequent changes in the expression of pheromone-producing enzymes underlie evolutionary transitions in chemical communication, and reflect changing regimes of sexual selection, which may have contributed to speciation among Drosophila

    Spitzer observations of extragalactic H II regions - III. NGC 6822 and the hot star, H II region connection

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    Using the short-high module of the Infrared Spectrograph on the Spitzer Space Telescope, we have measured the [S IV] 10.51, [Ne II] 12.81, [Ne III] 15.56, and [S III] 18.71-micron emission lines in nine H II regions in the dwarf irregular galaxy NGC 6822. These lines arise from the dominant ionization states of the elements neon (Ne++^{++}, Ne+^+) and sulphur (S3+^{3+}, S++^{++}), thereby allowing an analysis of the neon to sulphur abundance ratio as well as the ionic abundance ratios Ne+^+/Ne++^{++} and S3+^{3+}/S++^{++}. By extending our studies of H II regions in M83 and M33 to the lower metallicity NGC 6822, we increase the reliability of the estimated Ne/S ratio. We find that the Ne/S ratio appears to be fairly universal, with not much variation about the ratio found for NGC 6822: the median (average) Ne/S ratio equals 11.6 (12.2±\pm0.8). This value is in contrast to Asplund et al.'s currently best estimated value for the Sun: Ne/S = 6.5. In addition, we continue to test the predicted ionizing spectral energy distributions (SEDs) from various stellar atmosphere models by comparing model nebulae computed with these SEDs as inputs to our observational data, changing just the stellar atmosphere model abundances. Here we employ a new grid of SEDs computed with different metallicities: Solar, 0.4 Solar, and 0.1 Solar. As expected, these changes to the SED show similar trends to those seen upon changing just the nebular gas metallicities in our plasma simulations: lower metallicity results in higher ionization. This trend agrees with the observations.Comment: 22 pages, 13 figures. To be published in MNRAS. reference added and typos fixed. arXiv admin note: text overlap with arXiv:0804.0828, which is paper II by Rubin et al. (2008

    Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy

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    Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC’s systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.publishedVersio

    Identification of a Guanine Nucleotide Exchange Factor for Arf3, the Yeast Orthologue of Mammalian Arf6

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    Small G proteins of the Arf and Rab families are fundamental to the organisation and activity of intracellular membranes. One of the most well characterised of these G proteins is mammalian Arf6, a protein that participates in many cellular processes including endocytosis, actin remodelling and cell adhesion. Exchange of GDP for GTP on Arf6 is performed by a variety of guanine nucleotide exchange factors (GEFs), principally of the cytohesin (PSCD) and EFA6 (PSD) families. In this paper we describe the characterisation of a GEF for the yeast orthologue of Arf6, Arf3, which we have named Yel1 (yeast EFA6-like-1) using yeast genetics, fluorescence microscopy and in vitro nucleotide exchange assays. Yel1 appears structurally related to the EFA6 family of GEFs, having an N-terminal Sec7 domain and C-terminal PH and coiled-coil domains. We find that Yel1 is constitutively targeted to regions of polarised growth in yeast, where it co-localises with Arf3. Moreover the Sec7 domain of Yel1 is required for its membrane targeting and for that of Arf3. Finally we show that the isolated Yel1 Sec7 domain strongly stimulates nucleotide exchange activity specifically on Arf3 in vitro

    Identification of GBV-D, a Novel GB-like Flavivirus from Old World Frugivorous Bats (Pteropus giganteus) in Bangladesh

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    Bats are reservoirs for a wide range of zoonotic agents including lyssa-, henipah-, SARS-like corona-, Marburg-, Ebola-, and astroviruses. In an effort to survey for the presence of other infectious agents, known and unknown, we screened sera from 16 Pteropus giganteus bats from Faridpur, Bangladesh, using high-throughput pyrosequencing. Sequence analyses indicated the presence of a previously undescribed virus that has approximately 50% identity at the amino acid level to GB virus A and C (GBV-A and -C). Viral nucleic acid was present in 5 of 98 sera (5%) from a single colony of free-ranging bats. Infection was not associated with evidence of hepatitis or hepatic dysfunction. Phylogenetic analysis indicates that this first GBV-like flavivirus reported in bats constitutes a distinct species within the Flaviviridae family and is ancestral to the GBV-A and -C virus clades

    Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

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    The production of tt‟ , W+bb‟ and W+cc‟ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓΜ , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of tt‟t\overline{t}, W+bb‟W+b\overline{b} and W+cc‟W+c\overline{c} is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 ±\pm 0.02 \mbox{fb}^{-1}. The WW bosons are reconstructed in the decays W→ℓΜW\rightarrow\ell\nu, where ℓ\ell denotes muon or electron, while the bb and cc quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

    Measurement of CP violation parameters and polarisation fractions in Bs0→J/ψK‟∗0 {\mathrm{B}}_{\mathrm{s}}^0\to \mathrm{J}/\psi {\overline{\mathrm{K}}}^{\ast 0} decays

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    The first measurement of C ⁣P{C\!P} asymmetries in the decay Bs0→J/ψK‟∗(892)0{B_s^0\to J/\psi \overline{K}^{*}(892)^{0}} and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of 3.0 fb−13.0\,fb^{-1} of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of 77 and 8 TeV8\,\mathrm{TeV}. Together with constraints from B0→J/ψρ0{B^0\to J/\psi \rho^0}, the results are used to constrain additional contributions due to penguin diagrams in the C ⁣P{C\!P}-violating phase ϕs{{\phi}_{s}}, measured through Bs0{B_s^0} decays to charmonium.The first measurement of CP asymmetries in the decay Bs0→J/ψK‟∗(892)0 {B}_s^0\to J/\psi {\overline{\mathrm{K}}}^{\ast }{(892)}^0 and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of 3.0 fb^{−}^{1} of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Together with constraints from B0^{0} → J/ψ ρ0^{0}, the results are used to constrain additional contributions due to penguin diagrams in the CP -violating phase ϕs_{s} , measured through Bs0_{s}^{0} decays to charmonium.The first measurement of C ⁣P{C\!P} asymmetries in the decay Bs0→J/ψK‟∗(892)0{B_s^0\to J/\psi \overline{K}^{*}(892)^{0}} and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of 3.0 fb−13.0\,fb^{-1} of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of 77 and 8 TeV8\,\mathrm{TeV}. Together with constraints from B0→J/ψρ0{B^0\to J/\psi \rho^0}, the results are used to constrain additional contributions due to penguin diagrams in the C ⁣P{C\!P}-violating phase ϕs{{\phi}_{s}}, measured through Bs0{B_s^0} decays to charmonium
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